In this application for a Scientist Development Award for Clinicians (K- 20), we propose to study the effects of cocaine on the progression of HIV dementia (HIV associated cognitive / motor complex, or HIV-CMC) using modern neuroimaging techniques. A cross-sectional and longitudinal study in cocaine users and non-cocaine users with HIV-CMC will be performed. Cocaine is used illicitly by a large number of people, and has been shown to be immunotoxic in animals and possibly in man. Cocaine use is also a risk factor for HIV infection. Because HIV-CMC is caused by direct infection of the brain with HIV, we hypothesize that cocaine use leads to a more rapid progression of HIV-CMC in cocaine users compared to non cocaine users. Magnetic resonance imaging (MRI) will be performed to quantify changes in brain morphometry. As a quantitative measure of brain function, regional cerebral perfusion will be measured using single photon emission computed tomography (SPECT) and by a novel method, perfusion MRI. Finally, localized proton magnetic resonance spectroscopy (1H MRS) will be performed to assess cerebral biochemistry and neuronal viability. As a neurologist with some training in neuroimaging, the candidate (Linda Chang) is involved in a study on ethnic differences in the effects of cocaine use and in another study on the neurotoxicity of MDMA ("Ecstasy"). In order to conduct clinical research in drug abuse, the proposed study will allow her to combine her previous clinical and research experience, including dementia and AIDS, with the proposed supervised training in drug abuse and neuroimaging. The choice of preceptors reflects the interdisciplinary nature of the project; there is one preceptor for each area: drug neurotoxicity, neurochemistry, neurobehavior, and neuroimaging. This career and research plan will enable the applicant to develop as an independent investigator in the field of drug abuse research, with a focus on the application of state- of-the-art neuroimaging techniques to the study of drug-induced neurotoxicity.